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Expression of pleiotrophin in the prostate is androgen regulated and it functions as an autocrine regulator of mesenchyme and cancer associated fibroblasts and as a paracrine regulator of epithelia.

Orr B, Vanpoucke G, Grace OC, Smith L, Anderson RA, Riddick AC, Franco OE, Hayward SW, Thomson AA - Prostate (2010)

Bottom Line: Ptn transcripts and protein were localized by in situ and immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR.PTN also showed male enriched expression in fetal human male urethra versus female, and between wt male and ARKO male mice.Ptn protein was increased by testosterone in organ cultures of female rat VMP and in rat male urethra compared to female.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Reproductive Sciences Unit, The Queen's Medical Research Institute, Edinburgh, UK.

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Expression of Ptn mRNA in the mesenchyme of male and female UGT. Panel A: Comparison of transcript levels in the VMP, VSU and VP (P0) using Northern blot analysis. Transcript abundance was quantified using a phosphoimager and compared with levels expressed in the VP. The VMP exhibited a 2.6-fold enrichment of Ptn mRNA compared with the VSU (*P < 0.05) and the VP exhibited a 1.8-fold enrichment of Ptn mRNA compared with the VSU. Panel B: qRT-PCR analysis of Ptn mRNA expression in the male (m) and female (f) UGT at e17.5, and subsequent expression in the VP at P0, P4, P10, P28 and adult prostate. Ptn mRNA expression was significantly different in consecutive ages from e17.5 to P28 (a–eP < 0.001). Mean values were compared between the samples using one-way ANOVA followed by TUKEY multiple comparison. Panels C–F: Localization of Ptn mRNA using whole-mount in situ hybridization in the male and female UGT and VPs grown in vitro. Ptn mRNA expression pattern in female (C) and male (D). The male and female UGT are oriented with the bladder on the right. Ptn transcripts were localized to the VMP (C, arrow), and smooth muscle of the female UGT, and the VP (D, arrow), DP, smooth muscle and seminal vesicles of the male UGT. Panels E,F: Ptn mRNA distribution in VPs cultured in the absence or presence of testosterone. Ptn transcripts were localized to the mesenchyme of VP cultured ±T. The inset in the bottom right corner of panel F shows a magnification of VP + T; no antisense probe staining was observed in the epithelial ducts. Specimens hybridized with an antisense probe (purple/blue stain) are shown in each panel, whereas the sense probe is shown as an inset in the bottom left corner of each panel (no signal was observed using the control sense riboprobe). DP, dorsal prostate; URE, urethra; SM, smooth muscle; SV, seminal vesicles. The scale bar represents 200 µm in panels C and D, and 1 mm in panels E and F.
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fig01: Expression of Ptn mRNA in the mesenchyme of male and female UGT. Panel A: Comparison of transcript levels in the VMP, VSU and VP (P0) using Northern blot analysis. Transcript abundance was quantified using a phosphoimager and compared with levels expressed in the VP. The VMP exhibited a 2.6-fold enrichment of Ptn mRNA compared with the VSU (*P < 0.05) and the VP exhibited a 1.8-fold enrichment of Ptn mRNA compared with the VSU. Panel B: qRT-PCR analysis of Ptn mRNA expression in the male (m) and female (f) UGT at e17.5, and subsequent expression in the VP at P0, P4, P10, P28 and adult prostate. Ptn mRNA expression was significantly different in consecutive ages from e17.5 to P28 (a–eP < 0.001). Mean values were compared between the samples using one-way ANOVA followed by TUKEY multiple comparison. Panels C–F: Localization of Ptn mRNA using whole-mount in situ hybridization in the male and female UGT and VPs grown in vitro. Ptn mRNA expression pattern in female (C) and male (D). The male and female UGT are oriented with the bladder on the right. Ptn transcripts were localized to the VMP (C, arrow), and smooth muscle of the female UGT, and the VP (D, arrow), DP, smooth muscle and seminal vesicles of the male UGT. Panels E,F: Ptn mRNA distribution in VPs cultured in the absence or presence of testosterone. Ptn transcripts were localized to the mesenchyme of VP cultured ±T. The inset in the bottom right corner of panel F shows a magnification of VP + T; no antisense probe staining was observed in the epithelial ducts. Specimens hybridized with an antisense probe (purple/blue stain) are shown in each panel, whereas the sense probe is shown as an inset in the bottom left corner of each panel (no signal was observed using the control sense riboprobe). DP, dorsal prostate; URE, urethra; SM, smooth muscle; SV, seminal vesicles. The scale bar represents 200 µm in panels C and D, and 1 mm in panels E and F.

Mentions: Ptn was identified in the rat female VMP by LongSAGE transcriptional profiling with a ratio of 74:63 tags between the VMP/VSU 2. The VSU consists of VMP, smooth muscle and urethra and transcripts enriched or specific to the VMP are diluted in the VSU relative to pure VMP. Using Northern blot and qRT-PCR, Ptn transcript levels were ∼2.6-fold (Northern) (P < 0.05) and 1.5-fold (qRT-PCR, data not shown) higher in the VMP than VSU. The temporal expression of Ptn mRNA in the prostate was studied by qRT-PCR (Fig. 1B). Ptn was most abundant during the neonatal (P0) and perinatal period (P4, P10) and expression subsequently decreased until adulthood. There was also evidence of higher Ptn levels in males versus females at e17.5 (P < 0.001). To examine the spatial distribution of Ptn in the male and female UGT, whole-mount in situ hybridization was used to localize Ptn transcripts. Ptn mRNA was observed in the female in VMP and urethral stroma (Fig. 1C), and in the male in the prostatic mesenchyme (all lobes) and the urethral stroma (Fig. 1D). Additionally, to determine whether Ptn mRNA distribution was affected by testosterone, Ptn mRNA was localized in male VPs grown in culture ±T (Fig. 1E,F). Organ growth was stimulated by testosterone, and Ptn was present in mesenchymal cells throughout the VP, and the distribution of Ptn was similar between organs grown with or without testosterone. There was no evidence of epithelial Ptn expression (insets, Fig. 1E,F) though our studies do not rule out low level epithelial expression or expression within epithelial subsets.


Expression of pleiotrophin in the prostate is androgen regulated and it functions as an autocrine regulator of mesenchyme and cancer associated fibroblasts and as a paracrine regulator of epithelia.

Orr B, Vanpoucke G, Grace OC, Smith L, Anderson RA, Riddick AC, Franco OE, Hayward SW, Thomson AA - Prostate (2010)

Expression of Ptn mRNA in the mesenchyme of male and female UGT. Panel A: Comparison of transcript levels in the VMP, VSU and VP (P0) using Northern blot analysis. Transcript abundance was quantified using a phosphoimager and compared with levels expressed in the VP. The VMP exhibited a 2.6-fold enrichment of Ptn mRNA compared with the VSU (*P < 0.05) and the VP exhibited a 1.8-fold enrichment of Ptn mRNA compared with the VSU. Panel B: qRT-PCR analysis of Ptn mRNA expression in the male (m) and female (f) UGT at e17.5, and subsequent expression in the VP at P0, P4, P10, P28 and adult prostate. Ptn mRNA expression was significantly different in consecutive ages from e17.5 to P28 (a–eP < 0.001). Mean values were compared between the samples using one-way ANOVA followed by TUKEY multiple comparison. Panels C–F: Localization of Ptn mRNA using whole-mount in situ hybridization in the male and female UGT and VPs grown in vitro. Ptn mRNA expression pattern in female (C) and male (D). The male and female UGT are oriented with the bladder on the right. Ptn transcripts were localized to the VMP (C, arrow), and smooth muscle of the female UGT, and the VP (D, arrow), DP, smooth muscle and seminal vesicles of the male UGT. Panels E,F: Ptn mRNA distribution in VPs cultured in the absence or presence of testosterone. Ptn transcripts were localized to the mesenchyme of VP cultured ±T. The inset in the bottom right corner of panel F shows a magnification of VP + T; no antisense probe staining was observed in the epithelial ducts. Specimens hybridized with an antisense probe (purple/blue stain) are shown in each panel, whereas the sense probe is shown as an inset in the bottom left corner of each panel (no signal was observed using the control sense riboprobe). DP, dorsal prostate; URE, urethra; SM, smooth muscle; SV, seminal vesicles. The scale bar represents 200 µm in panels C and D, and 1 mm in panels E and F.
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fig01: Expression of Ptn mRNA in the mesenchyme of male and female UGT. Panel A: Comparison of transcript levels in the VMP, VSU and VP (P0) using Northern blot analysis. Transcript abundance was quantified using a phosphoimager and compared with levels expressed in the VP. The VMP exhibited a 2.6-fold enrichment of Ptn mRNA compared with the VSU (*P < 0.05) and the VP exhibited a 1.8-fold enrichment of Ptn mRNA compared with the VSU. Panel B: qRT-PCR analysis of Ptn mRNA expression in the male (m) and female (f) UGT at e17.5, and subsequent expression in the VP at P0, P4, P10, P28 and adult prostate. Ptn mRNA expression was significantly different in consecutive ages from e17.5 to P28 (a–eP < 0.001). Mean values were compared between the samples using one-way ANOVA followed by TUKEY multiple comparison. Panels C–F: Localization of Ptn mRNA using whole-mount in situ hybridization in the male and female UGT and VPs grown in vitro. Ptn mRNA expression pattern in female (C) and male (D). The male and female UGT are oriented with the bladder on the right. Ptn transcripts were localized to the VMP (C, arrow), and smooth muscle of the female UGT, and the VP (D, arrow), DP, smooth muscle and seminal vesicles of the male UGT. Panels E,F: Ptn mRNA distribution in VPs cultured in the absence or presence of testosterone. Ptn transcripts were localized to the mesenchyme of VP cultured ±T. The inset in the bottom right corner of panel F shows a magnification of VP + T; no antisense probe staining was observed in the epithelial ducts. Specimens hybridized with an antisense probe (purple/blue stain) are shown in each panel, whereas the sense probe is shown as an inset in the bottom left corner of each panel (no signal was observed using the control sense riboprobe). DP, dorsal prostate; URE, urethra; SM, smooth muscle; SV, seminal vesicles. The scale bar represents 200 µm in panels C and D, and 1 mm in panels E and F.
Mentions: Ptn was identified in the rat female VMP by LongSAGE transcriptional profiling with a ratio of 74:63 tags between the VMP/VSU 2. The VSU consists of VMP, smooth muscle and urethra and transcripts enriched or specific to the VMP are diluted in the VSU relative to pure VMP. Using Northern blot and qRT-PCR, Ptn transcript levels were ∼2.6-fold (Northern) (P < 0.05) and 1.5-fold (qRT-PCR, data not shown) higher in the VMP than VSU. The temporal expression of Ptn mRNA in the prostate was studied by qRT-PCR (Fig. 1B). Ptn was most abundant during the neonatal (P0) and perinatal period (P4, P10) and expression subsequently decreased until adulthood. There was also evidence of higher Ptn levels in males versus females at e17.5 (P < 0.001). To examine the spatial distribution of Ptn in the male and female UGT, whole-mount in situ hybridization was used to localize Ptn transcripts. Ptn mRNA was observed in the female in VMP and urethral stroma (Fig. 1C), and in the male in the prostatic mesenchyme (all lobes) and the urethral stroma (Fig. 1D). Additionally, to determine whether Ptn mRNA distribution was affected by testosterone, Ptn mRNA was localized in male VPs grown in culture ±T (Fig. 1E,F). Organ growth was stimulated by testosterone, and Ptn was present in mesenchymal cells throughout the VP, and the distribution of Ptn was similar between organs grown with or without testosterone. There was no evidence of epithelial Ptn expression (insets, Fig. 1E,F) though our studies do not rule out low level epithelial expression or expression within epithelial subsets.

Bottom Line: Ptn transcripts and protein were localized by in situ and immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR.PTN also showed male enriched expression in fetal human male urethra versus female, and between wt male and ARKO male mice.Ptn protein was increased by testosterone in organ cultures of female rat VMP and in rat male urethra compared to female.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Reproductive Sciences Unit, The Queen's Medical Research Institute, Edinburgh, UK.

Show MeSH
Related in: MedlinePlus